Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously we isolated a tetrasaccharide-serine and a hexasaccharide-serine from the carbohydrate-protein linkage region of porcine intestinal heparin after digestion with a mixture of Flavobacterium heparinase and heparitinases I and II (Sugahara, K., Yamada, S., Yoshida, K., de Waard, P., and Vliegenthart, J.F.G. (1992) J. Biol. Chem. 267, 1528-1533). In this study four longer carbohydrate sequences (I-IV) attached to Ser or a dipeptide (Ser-Gly or Gly-Ser), which accounted for at least 18.2% of the total linkage region, were isolated from the same heparin preparation after digestion with heparinase only. IV was successfully isolated only after subsequent digestion with glycuronate-2-sulfatase. Their structures were determined by chemical and enzymatic analyses and 1H NMR spectroscopy and found to be the following octa- and decasaccharide sequences attached to Ser in a molar ratio of 1.1:2.3:1.0:1.3: delta HexA(2S)alpha 1-4GlcN(NS,6S)alpha 1-4GlcA beta 1-4GlcNAc alpha 1-4- GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser (I), delta HexA(2S)alpha 1- 4GlcN(NS,6S)alpha 1-4IdoA alpha 1-4GlcNAc alpha 1-4GlcA beta 1- 3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser (II), delta HexA(2S)alpha 1- 4GlcN(NS,6S)alpha 1- 4IdoA alpha 1-4GlcNAc alpha 1-4GlcA beta 1-4GlcNAc-alpha 1- 4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser (III), delta HexA alpha 1-4GlcN(NS,6S)alpha 1-4IdoA alpha 1-4GlcNAc(6S)alpha 1- 4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser (IV) (delta HexA, GlcA, IdoA, and GlcN represent 4,5-unsaturated hexuronic acid, D-glucuronic acid, L-iduronic acid, and D-glucosamine, whereas 2S, 6S, and NS stand for 2-sulfate, 6-sulfate, and N-sulfate, respectively). I and II contained 1 mol of Gly in addition to Ser. The four structures indicate that sulfation in heparin chains takes place on the monosaccharide residues located in closer vicinity to the core protein than found for heparan sulfate chains and that there exist at least several heparin subclass chains with different linkage region structures. The significance of the isolated structures is discussed in relation to the biological functions and the biosynthetic mechanisms of heparin.
 ...
PMID:Structure determination of the octa- and decasaccharide sequences isolated from the carbohydrate-protein linkage region of porcine intestinal heparin. 755 27

To understand the molecular basis of metachromatic leukodystrophy (MLD) in Japanese patients, we analyzed the presence of three known mutant arylsulfatase A (ASA) alleles in 9 Japanese patients with MLD. Two of these mutant alleles (designated 609A and 2381T) were reported to be relatively frequent in a sample of predominantly Caucasian MLD. The other allele, with a substitution of Gly-99 by Asp (allele 445A), had been identified in a Japanese adult form of MLD in a heterozygous combination. We have found that allele 445A has a moderately high incidence among Japanese patients with MLD, and that homozygosity results in the late-infantile form. Neither allele 609A nor 2381T was found in Japanese patients examined in this study. Analysis on the nucleotide sequence of the ASA genes from another late-infantile MLD patient revealed the presence of a previously unreported G-to-A mutation at the 1,070th nucleotide of the ASA gene (designated 1070A). This results in a substitution of Gly-245 by Arg. This 1070A mutation was also found heterozygously in a juvenile MLD patient. When the 1070A mutation was introduced into the ASA cDNA and evaluated by transient expression studies, no enzyme activity was induced. These results suggest that Japanese MLD patients have a different distribution of ASA mutations from that found in a predominantly Caucasian population.
 ...
PMID:Mutations in the arylsulfatase A gene of Japanese patients with metachromatic leukodystrophy. 810 Oct 83

Two novel mutations in the arylsulfatase A (ASA) gene from a Japanese patient with the late-infantile form of metachromatic leukodystrophy (MLD) were identified. One mutation was a G to C transversion at nucleotide 608 of the ASA gene (designated 608C) located at the 3' end of exon 2, which resulted in an amino acid substitution of Gln 153 to His. Although the 608 mutation resulted in a change in the exon-intron boundary consensus sequence, analysis of cDNA from the patient did not reveal the presence of aberrant splicing. The second mutation, a G to T transversion at nucleotide 1572 in exon 5 (designated 1572T), resulted in an amino acid substitution of Gly 308 to Val. This could potentially result in a conformational change in ASA protein structure. The patient was heterozygous for these two new mutations which were not present in 18 Japanese MLD alleles examined. A transient expression study in COS-1 cells showed no residual activity in either mutation. These results indicate that the 608C and 1572T mutations are responsible for the occurrence of the late-infantile form of MLD.
 ...
PMID:Two novel mutations in a Japanese patient with the late-infantile form of metachromatic leukodystrophy. 889 Dec 36

Pro CCK was expressed in an L cell line engineered to express PC1 and the products secreted into the media were characterized by a combination of RIA, gel filtration and HPLC. PC1 released from L cells, cleaved pro CCK generating the amino terminal pro peptide. PC1 also generated a peptide which after carboxypeptidase B treatment, was detected with an antiserum specific for CCK Gly. Neither of these peptides was found in media from L cells expressing pro CCK alone. This CCK Gly immunoreactive peptide was similar in size to CCK 8, and after treatment with arylsulfatase and carboxypeptidase B, it co-eluted on HPLC with unsulfated CCK 8 Gly. These results agree with previous studies which support a role for PC1 in generation of CCK 8. This is the first demonstration that PC1 acting alone is able to cleave pro CCK liberating the amino terminal pro peptide and a glycine and arginine extended CCK 8 which is the immediate precursor of CCK 8 amide.
 ...
PMID:Prohormone convertase 1 (PC1) when expressed with pro cholecystokinin (pro CCK) in L cells performs three endoproteolytic cleavages which are observed in rat brain and in CCK-expressing endocrine cells in culture, including the production of glycine and arginine extended CCK8. 970 61

Metachromatic leukodystrophy (MLD) is an autosomal recessive, lysosomal storage disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). The aim of the present study was to identify the molecular basis of MLD in Tunisian population. Two Tunisian patients with late infantile MLD were studied. Both patients were homozygous for a new missense mutation that causes a substitution of Trp in Gly p.W124G. This is the first mutation of ARSA gene described in Tunisian population.
 ...
PMID:Identification of a new Arylsulfatase A (ARSA) gene mutation in Tunisian patients with metachromatic leukodystrophy (MLD). 1969 91